1. De Novo and Restenotic Coronary Lesions
Clinical and Angiographic Outcomes After Use of Sr-90 Beta Radiation for the Treatment of
De Novo and Restenotic Coronary Lesions
Richard E. Kuntz
Burton Speiser, Michel Joyal/Raoul Bonan & Andre Arseneault, Gary Neiss/David Cox & Mark Kirsch, Warren Laskey & Mohan Suntharalingham, Charles Wilmer/Charles Brown & Frederick Schwaibold, Sigmund Silber & Peter von Rottkay, David Fischman & Michael Savage,
and Stuart Pocock & Mona Abdalla
for the Beta-Cath System Trial Investigators
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

2. Background
Beta radiation using 90Strontium/ 90Yttrium (Sr-90), and Phosphorous-32 significantly reduced angiographic and clinical recurrence after PTCA for in-stent restenosis in two randomized trials (START and INHIBIT), confirming earlier beneficial effects shown with gamma radiation, Iridium-192 (SCRIPPS, WRIST, GAMMA-I).
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

3. Purpose
To assess the safety and effectiveness of beta radiation in patients with de novo coronary lesions using a 30mm 90Sr/90Y source train in conjunction with:
Stand alone balloon angioplasty, or
Provisional stent placement in which balloon angioplasty was suboptimal
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

4. “Radiation Source Train”
The Beta-Cath System
Transfer Device
Containing
“Radiation Source Train”
Coronary Artery
“Delivery Catheter”

5. Patient undergoes PTCA (n=1100) Suboptimal PTCA result
Original Trial Design – July ‘97
Patient undergoes PTCA (n=1100)
Optimal PTCA result
Stand-alone
PTCA Branch
Suboptimal PTCA result
Provisional Stent arm
Randomize
Randomize
Placebo
Sr-90
Placebo
Sr-90
Stent
as needed
No planned
intervention
Stent
deployment

6. Trial Design Primary Efficacy Endpoint:
8-Month TVF (Target Vessel Failure : death, MI, TVR)
Secondary Efficacy Endpoints:
8-Month angiographic restenosis, MLD and late loss at target site
Safety Endpoints:
8-Month MACE (Major Adverse Cardiac Events : Death, MI, emergent CABG, TVR) and aneurysm formation

7. Sample Size Determination
Clinical Restenosis: Designed to show a 32% treatment effect in the overall trial, assuming a 22% 8-month TVF rate in the placebo group and a 15% 8-month TVF rate in the treatment group (a = 0.05; b = 0.20) with a study enrollment of 1100 patients
Angiographic Restenosis: Designed to detect 0.2 mm difference between active and placebo arms in each branch (balloon angioplasty and stent branches, a = 0.05; b = 0.20), assuming an 80% angiographic follow-up rate, with a minimum enrollment of 480 patients per branch
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

8. Trial Design Trial Initiated: July 1997 Enrollment: 1,100 patients
Enrollment Completion:
September 1999
Site Participation:
59 (US & Europe)
Trial Design:
Randomized, Triple-Masked
Principal Investigators:
R. Kuntz, MD (Cardiology)
B. Speiser, MD (Rad Onc)

9. Sample Size Expansion
NOV DSMB reported an unexpectedly high level of late stent thrombosis.
Sponsor recommended minimum 60 days antiplatelet therapy (APT)
MAR DSMB recommended extension of trial with a new branch to replicate the Provisional Stent Branch with extended APT, minimum of 90 days.
N = 1455
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)
Stand Alone
PTCA Branch
(n=504)
Provisional
Stent Branch
(n= 499)
Provisional
Stent Branch
>60/90 days APT
(n=452)

10. Trial Design Data Coordinating and Statistical Analysis Center
CDAC / Harvard Clinical Research Institute
London School of Hygiene/Tropical Medicine:
Stuart Pocock and Mona Abdalla
Angiographic Laboratory
Thomas Jefferson University:
David Fischman, MD; Michael Savage, MD
IVUS Core Laboratory
CRI: Neil Weismann, MD
EKG Core Laboratory
CDAC: Peter Zimetbaum, MD
DSMB Committee
Chairman: Thomas Ryan, MD
Clinical Events Committee
Chairman: David Cohen, MD
Sponsor
Novoste Corporation

11. INCLUSION CRITERIA EXCLUSION CRITERIA
Single lesion, single vessel intervention
De novo or restenotic > 50% (by visual assessment)
Target lesion in vessels between 2.7 and 4.0 mm RVD
Target lesion length treatable with 20 mm balloon with the 30 mm Source Train
PTCA Stand-alone Enrollment
Stable lumen <30% DS
Absence of thrombus, spasm,
or dissection
EXCLUSION CRITERIA
Multi-vessel coronary intervention
Unprotected left main disease
Prior Chest Radiotherapy
Provisional Stent Enrollment
Stable lumen  30 to 50% DS
Absence of thrombus, spasm, or significant dissection
Stent mounted on balloon  24mm
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

12. Dose Prescription
Reference vessel diameter (RVD) was determined visually after completion of coronary intervention
Dose prescription point 2 mm from center of source axis:
16.1 Gy* in RVD > < 3.3 mm
20.7 Gy* in RVD > <4.0mm
90Sr/90Y has a 28 year half-life, and short treatment time of 3-5 minutes
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)
*NIST dose recalibration, March 2000

13. Overall Baseline Demographics
Total cohort
Sr n = 744
Placebo
n = 711
Age, yrs.
61.0
60.7
Men, %
73.3
73.7
Diabetes, %
22.2
23.2
Smoking, %
27.0
26.8
Restenotic, %
8.2
7.5
Prior CABG, %
9.8
9.0
LVEF, %
57.4
57.5

14. Baseline Angiographic Findings
PTCA
Sr Placebo
Stent
Sr Placebo
Stent (>60d)
RVD, mm
2.98
3.00
3.09
3.05
3.07
3.01
Pre - MLD, mm
0.85
0.84
0.86
0.88
0.89
Pre – DS, %
71.3
72.3
71.7
71.2
71.5
70.8
Lesion Length, mm
11.9
12.3
12.6
12.7
12.5
12.8

15. Follow-up Percent Compliance
Sr Placebo
PTCA
264
240
Clinical
95.8%
95.4%
Angiographic
81.8%
87.9%
Stent
252
247
97.2%
97.6%
79.8%
82.2%
Stent  60d
228
224
93.4%
93.8%
81.1%
82.1%

16. Major Adverse Events – In-Hospital%
PTCA
Sr Placebo
n= n=240
Stent
Sr Placebo
n= n=240
Stent (>60d)
Sr Placebo
n= n=240
Death
0.0
0.4
0.5
Q Wave MI
0.8
Non-Q Wave MI
1.1
1.7
3.2
2.0
1.3
3.6
Emerg. CABG
TVR
0.9
2.2
Any MACE
1.5
2.5
2.8
4.9
Abrupt Closure --
Stent Occlusion

17. Late Treatment Site Thrombosis (thrombosis >30 days)
Placebo
Sr-90 %
p=0.18
p<0.001
p=0.98
Both were bailout stents
This is the Sample Column Chart slide.
To create this particular slide, copy and paste the sample in the Slide Sorter view as follows:
Select View / Slide Sorter
Highlight the Sample Column Chart page and select Edit / Copy
Place the courser where you want the new slide to be and select Edit / Paste
Double-click on the pasted-in slide to return to Slide view
To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here.
When you are finished making your changes, select File / Exit and return to… from the menu bar.
THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph.
n = 2
n = 17
n = 3
n = 3

18. Clinical Outcome Analysis – New Cohort following DSMB recommendation
PTCA
(n=504)
Stent
(n= 499)
Stent
>60d APT
(n=452)
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)
New Cohort

19. 8 Mo Clinical Outcomes – New Cohort n=956
(%)
This is the Sample Column Chart slide.
To create this particular slide, copy and paste the sample in the Slide Sorter view as follows:
Select View / Slide Sorter
Highlight the Sample Column Chart page and select Edit / Copy
Place the courser where you want the new slide to be and select Edit / Paste
Double-click on the pasted-in slide to return to Slide view
To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here.
When you are finished making your changes, select File / Exit and return to… from the menu bar.
THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph.
 12 %
p=0.37
 10 %
p=0.41
 9 %
p=0.40
Heterogeneity test
p=0.09
p=0.19
p=0.08

21. 8 Month Angiographic Outcomes
(%)
Sr-90
Placebo
This is the Sample Column Chart slide.
To create this particular slide, copy and paste the sample in the Slide Sorter view as follows:
Select View / Slide Sorter
Highlight the Sample Column Chart page and select Edit / Copy
Place the courser where you want the new slide to be and select Edit / Paste
Double-click on the pasted-in slide to return to Slide view
To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here.
When you are finished making your changes, select File / Exit and return to… from the menu bar.
THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph.
 38%
p=0.003
 14%
p=0.27
 36%
p=0.01
 21%
p=0.06
Note: No late aneurysms detected
PTCA Group
Stent (>60d) Group

22. Secondary Analysis

23. Clinical Outcome Analysis – All Stent Cohort
PTCA
(n=504)
Stent
(n= 499)
Stent
>60d APT
(n=452)
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)
All Stent Cohort

24. 8 Mo Angiographic Outcomes – All Stent
(%)
Sr-90, n=380
Placebo, n=384
This is the Sample Column Chart slide.
To create this particular slide, copy and paste the sample in the Slide Sorter view as follows:
Select View / Slide Sorter
Highlight the Sample Column Chart page and select Edit / Copy
Place the courser where you want the new slide to be and select Edit / Paste
Double-click on the pasted-in slide to return to Slide view
To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here.
When you are finished making your changes, select File / Exit and return to… from the menu bar.
THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph.
 29%
p=0.004
 30%
p=0.004

25. 8 Mo Clinical Outcomes – All Stent
(%)
This is the Sample Column Chart slide.
To create this particular slide, copy and paste the sample in the Slide Sorter view as follows:
Select View / Slide Sorter
Highlight the Sample Column Chart page and select Edit / Copy
Place the courser where you want the new slide to be and select Edit / Paste
Double-click on the pasted-in slide to return to Slide view
To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here.
When you are finished making your changes, select File / Exit and return to… from the menu bar.
THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph.
 59 %
p=0.001
 54 %
p=0.001
 60 %
p=0.001
Heterogeneity test
p=0.06
p=0.02
p=0.01

26. Clinical Outcome Analysis – PTCA
Stent
(n= 499)
Stent
>60d APT
(n=452)
This is the Bulleted List slide.
To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left)
The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide.
If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page.
Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows:
Choose View / Master / Slide Master from your menu.
Select the text at the bottom of the slide and type in a short version of your presentation title.
Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

27. 8 Mo Clinical Outcomes – PTCA
(%)
This is the Sample Column Chart slide.
To create this particular slide, copy and paste the sample in the Slide Sorter view as follows:
Select View / Slide Sorter
Highlight the Sample Column Chart page and select Edit / Copy
Place the courser where you want the new slide to be and select Edit / Paste
Double-click on the pasted-in slide to return to Slide view
To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here.
When you are finished making your changes, select File / Exit and return to… from the menu bar.
THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph.
 35%
p=0.07
 28%
p=0.12
 30%
p=0.06

29. Conclusions
The Beta-Cath™ System trial is the first and largest prospective, randomized, blinded placebo-controlled multi-center trial that investigated the use of vascular brachytherapy (VBT) for the prevention of restenosis in de novo lesions.
This study was the first to identify the higher-than- expected rate of late stent thrombosis when radiation was used with new stent implantation, and was the first to solve it with extension of adjunctive anti-platelet therapy.

30. Conclusions
The primary clinical endpoint, Target Vessel Failure (TVF), was not shown to be significantly lower in the combined radiation arms compared with combined placebo arms.
Secondary analyses:
Beta radiation in the PTCA branch:
34.6% reduction for Sr-90 in TVF/MACE rate, p=0.06
37.6% reduction for Sr-90 in lesion segment restenosis rate, p=0.003
Disparate results in angiographic restenosis in the combined Stent branches:
28.9% reduction for Sr-90 in lesion segment restenosis rate, p=0.004
30% increase for Sr-90 in the analysis segment, p=0.004

31. Conclusions
The paradox of positive treatment effect for Sr-90 seen in ALL lesion segment analysis and the negative treatment effect of Sr-90 seen in the Stent analysis segment likely explains the negative treatment effect of Sr-90 on clinical restenosis in stents, and merits further investigation.
Geographic Miss (inadequate radiation coverage of the interventional injury) may have contributed to the negative results of Sr-90.
The overall positive results in the lesion segment analysis and the strong trends in the clinical outcomes in the PTCA branch suggests a potential role for Sr-90 radiation in the treatment of de novo coronary lesions if the increase in restenosis in the “analysis segment” can be solved.